Rapid and Concomitant Gut Microbiota and Endocannabinoidome Response to Diet-Induced Obesity in Mice

Lacroix, Sébastien; Pechereau, Florent; Leblanc, Nadine; Boubertakh, Besma; Houde, Alain; Martin, Cyril; Flamand, Nicolas; Silvestri, Cristoforo; Raymond, Frédéric; Marzo, Vincenzo Di; Veilleux, Alain

doi:10.1128/msystems.00407-19

Cited by 61 publications

(69 citation statements)

References 38 publications

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“…More recently, time-and gut segment-specific microbiome disturbances concomitant to modifications of intestinal and circulating eCBome mediators have been found after 56 days of HFHS diet, thus suggesting the involvement of the microbiota-gut-eCB(ome) axis in diet-induced glucose intolerance, obesity and other metabolic disturbances. Elevation of AEA, in both ileum and plasma, and 2-AG, in plasma, as well as alterations in several other NAEs and 2-acylglycerols were reported by comparison with low-fat, low-sucrose (LFLS) diet with identical fiber and fatty acid percent compositions [27]. In the ileum, HFHS diet-induced temporal changes in AEA levels, and hence possibly in CB1 tone, inversely correlated with the abundance of metabolically beneficial gut commensal microorganisms, such as Akkermanisa, Barnesiella, Eubacterium, Adlercreutzia, and Propionibacterium spp., in some cases independently of body weight changes.…”

Section: Microbiota-endocannabinoidome-gut Axismentioning

confidence: 99%

“…Seminal studies demonstrated that: (i) infusion of LPS had effects similar to those of a high-fat diet (HFD) at increasing fasting glycaemia, insulinemia and whole-body, hepatic and adipose tissue weight gain; (ii) LPS and endocannabinoid levels are positive correlated [16,17], also because of the downregulation of gene expression of acid amide hydrolase (FAAH, the enzyme that degrades AEA) and N-acylethanolamines (NAEs, congeners of AEA) [18]; and (iii) gut dysbiosis and the eCB system are both involved in adipogenesis through a LPS-dependent neuroinflammatory mechanism under obesity-related conditions. In the past several years, our group and others have provided evidence that obesity is associated with increased eCB tone in the brain and plasma, altered expression of cannabinoid receptor 1 (CB1 mRNA) and increased eCB levels in the adipose tissue, liver, muscle and pancreas [19][20][21][22][23][24][25][26][27][28]. Although genetic and pharmacological impairments of peripheral CB1 receptor have been shown to protect against the development of obesity, steatosis and related inflammation [29,30], the molecular link between gut dysbiosis, the eCB system and metabolic disorders associated with obesity remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

Forte

Fernández-Rilo

Palomba

et al. 2020

IJMS

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The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota–gut–brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the “expanded endocannabinoid (eCB) system” or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.

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Section: Microbiota-endocannabinoidome-gut Axismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

Forte

Fernández-Rilo

Palomba

et al. 2020

IJMS

Self Cite

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“…The gut microbiota have been identified as an environmental factor that markedly affects digestive capacity, nutritional absorption, energy balance, and body fat accumulation in mammals. [81][82][83][84] Germ-free animal and fecal microbial transplantation provide direct insights into the function of gut microbiota in host lipid metabolism and obesity development. Germ-free mice fail to gain additional weight and remain lean compared to conventionally raised counterparts.…”

Section: Gut Microbiotamentioning

confidence: 99%

Circadian rhythms and obesity: Timekeeping governs lipid metabolism

Yao

et al. 2020

Journal of Pineal Research

111

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Almost all living organisms have evolved autoregulatory transcriptional‐translational feedback loops that produce oscillations with a period of approximately 24‐h. These endogenous time keeping mechanisms are called circadian clocks. The main function of these circadian clocks is to drive overt circadian rhythms in the physiology of the organisms to ensure that main physiological functions are in synchrony with the external environment. Disruption of circadian rhythms caused by genetic or environmental factors has long‐term consequences for metabolic health. Of relevance, host circadian rhythmicity and lipid metabolism are increasingly recognized to cross‐regulate and the circadian clock‐lipid metabolism interplay may involve in the development of obesity. Multiple systemic and molecular mechanisms, such as hormones (ie, melatonin, leptin, and glucocorticoid), the gut microbiome, and energy metabolism, link the circadian clock and lipid metabolism, and predictably, the deregulation of circadian clock‐lipid metabolism interplay can increase the risk of obesity, which in turn may exacerbate circadian disorganization. Feeding time and dietary nutrients are two of key environmental Zeitgebers affecting the circadian rhythm‐lipid metabolism interplay, and the influencing mechanisms in obesity development are highlighted in this review. Together, the characterization of the clock machinery in lipid metabolism aimed at producing a healthy circadian lifestyle may improve obesity care.

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“…The gut microbiota is strongly shaped by HFDs, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions, especially in terms of Firmicutes and Bacteroidetes abundances (18)(19)(20)(21)(22)(23)(24)(25). Interestingly, several reports have revealed that the gut microbiota and its metabolites exhibit circadian rhythms, which are driven by HFDs (26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

Yin

Han

et al. 2020

mSystems

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Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice. IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.

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Rapid and Concomitant Gut Microbiota and Endocannabinoidome Response to Diet-Induced Obesity in Mice

Cited by 61 publications

References 38 publications

Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

Circadian rhythms and obesity: Timekeeping governs lipid metabolism

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

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